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is supported by the fact that global white matter changes
reflecting demyelination and thus disrupting trans-synaptic
communications have been implicated as a possible
mechanism underlying postirradiation brain injury causing
cognitive deficits . Similarly, a diffusion tensor
imaging-based study in children with posterior fossa tumors
revealed that disruption of cerebellothalamocerebral path-
ways following irradiation were associated with poorer
working memory, a core cognitive skill involved in com-
plex cognitive functions including IQ and academics
The same authors stated that diffuse white matter changes
in the posterior fossa following irradiation and disruption of
multiple other pathways connecting cerebellum to supra-
tentorial structures may have been responsible for deficits.
Linguistic skills such as reading and spelling were more
vulnerable than math skills in our cohort as shown by the
decline in these group mean scores over time. This finding
is contrary to the greater math impairment observed in
children treated with cranial irradiation but may reflect
greater specificity of localized cerebellar insult following
irradiation . The frontal, parietal, temporal, and oc-
cipital regions have been reported to be activated in
response to tasks eluding orthographic, phonological, and
semantic processes involved in reading . The posterior
cerebellar regions have now been added to this list
Cerebellar hemispheric regions adjacent to posterior supe-
rior fissure are bilaterally being activated during phono-
logical assembly and deep nuclear regions on the right
activated during semantic processing Riva et al in
their study of children with cerebellar tumors reported poor
naming and comprehension abilities that were more pro-
nounced in right cerebellar lesions. Most of our patients
had midline tumors. Minimal dose differences in right and
left cerebellar hemispheres limited our ability to test this
lateralization effect .
Cerebellar involvement in mathematical calculations has
been documented and is thought to rely on its connectivity
with frontal brain regions WIAT math mean scores on
follow-up, however, were unchanged as reported earlier
but children receiving higher-than-average population
mean doses to infratentorial brain and more specifically to
posterior cerebellum had steeper declines in all three aca-
demic achievement scores over time, showing a deleterious
effect of higher cerebellar doses on these skills.
Among the various clinical covariates studied, younger
children had lower baseline IQ scores, but age effect was not
evident at 5 years after CRT, which could be attributed to the
sparing effect of conformal irradiation that probably does not
halt their recovery from perioperative insults
Consistent with earlier reports, the deleterious negative as-
sociation of severe hydrocephalus on cognition was evident
and the reversible nature of this effect was replicated by the
loss of this negative association with the longitudinal trends
IQ scores are age standardized to account for change in
performance associated with typical development. The pos-
itive correlation between age at time of irradiation and
baseline IQ scores likely reflects the protective effect of age
with respect to potential insults encountered prior to irradi-
ation (eg, surgical interventions, chemotherapy).
Although mean supratentorial doses were not found to
affect any longitudinal cognitive trend in this analysis, we
cannot outwardly refute this aspect as cranial doses as low
as 18 Gy have been implicated in effects on cognition in
children with acute lymphoid leukemia , and mean
supratentorial dose for our cohort was approximately
14 Gy. Our previous analysis revealed that supratentorial
volumes receiving doses as low as 0 to 5 Gy have negative
effects on IQ . This difference could have been because
of the different parameter used in present analysis (ie, mean
dose as opposed to the volume receiving dose between
0 and 5 Gy) Long-term detrimental effects of surgery
cannot be completely excluded. Associations of long term
cognitive deficits with postoperative acute cerebellar insults
like cerebellar mutism have been suggested in the literature
We realize that the academic performances
assessed are known to be influenced by other behavioral
and environmental factors such as prolonged school ab-
sences which could not be accounted for but would not be
expected to affect academic domains differentially.
Conclusions
In this relatively homogenous cohort, we were able to
demonstrate that high-dose cerebellar irradiation negatively
influenced the longitudinal trend of multiple cognitive
measures and mirrored the functional topography of cere-
bellum. Our goal was not to prove whether the cerebellum
was directly involved in cognition but rather to determine
the contribution of cerebellar irradiation on long-term
cognitive effects realizing that the cerebellum is part of a
neural network.
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Merchant et al. International Journal of Radiation Oncology Biology Physics 552